CN102600140A - Composite for treating vascular hypertension - Google Patents
Composite for treating vascular hypertension Download PDFInfo
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- CN102600140A CN102600140A CN2012100670964A CN201210067096A CN102600140A CN 102600140 A CN102600140 A CN 102600140A CN 2012100670964 A CN2012100670964 A CN 2012100670964A CN 201210067096 A CN201210067096 A CN 201210067096A CN 102600140 A CN102600140 A CN 102600140A
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- Prior art keywords
- taurine
- candesartan cilexetil
- compositions
- hypertension
- grams
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 206010020772 Hypertension Diseases 0.000 title abstract description 15
- 230000002792 vascular Effects 0.000 title abstract description 5
- 239000002131 composite material Substances 0.000 title abstract 3
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims abstract description 60
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229960004349 candesartan cilexetil Drugs 0.000 claims abstract description 31
- 229960003080 taurine Drugs 0.000 claims abstract description 30
- 239000003814 drug Substances 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims description 34
- 150000001875 compounds Chemical class 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000002195 synergetic effect Effects 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 11
- 230000036772 blood pressure Effects 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 230000035487 diastolic blood pressure Effects 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 206010010164 Hypertension complications Diseases 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000002220 antihypertensive agent Substances 0.000 description 3
- 229940127088 antihypertensive drug Drugs 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000000890 drug combination Substances 0.000 description 3
- 230000002526 effect on cardiovascular system Effects 0.000 description 3
- -1 hydroxypropyl Chemical group 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000002053 C09CA06 - Candesartan Substances 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 229940097320 beta blocking agent Drugs 0.000 description 2
- 229960000932 candesartan Drugs 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 235000012000 cholesterol Nutrition 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000035488 systolic blood pressure Effects 0.000 description 2
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 2
- 210000001364 upper extremity Anatomy 0.000 description 2
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 description 1
- 229940097420 Diuretic Drugs 0.000 description 1
- 206010013754 Drug withdrawal syndrome Diseases 0.000 description 1
- 208000019025 Hypokalemia Diseases 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 201000004239 Secondary hypertension Diseases 0.000 description 1
- 229940121792 Thiazide diuretic Drugs 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 206010013663 drug dependence Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000003516 hyperlipidaemic effect Effects 0.000 description 1
- 239000005555 hypertensive agent Substances 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 235000005955 light diet Nutrition 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 235000008935 nutritious Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 208000024896 potassium deficiency disease Diseases 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000003716 rejuvenation Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000011117 substance-related disease Diseases 0.000 description 1
- 239000003451 thiazide diuretic agent Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a medicine composite for treating vascular hypertension, which is characterized by comprising candesartan cilexetil and taurine. By means of compatibility of the candesartan cilexetil and the taurine, an unexpected synergistic effect is generated, and the composite is clinical medication with high curative effect and low side effects for patients suffering from hypertension.
Description
Technical field: the present invention relates to a kind of pharmaceutical composition of treating vascular hypertension.
Background technology: hypertension is common cardiovascular and cerebrovascular disease, can be divided into two kinds of constitutional and Secondary cases.Along with improving constantly of human living standard; The change of diet structure, and the increase of life stress, hypertension incidence rate have the tendency that progressively raises; And be rejuvenation trend; Hypertension can cause the infringement of organs such as the heart, brain, kidney, and with sugar, disorders of lipid metabolism and diabetes confidential relation is arranged, entail dangers to patient life when serious.Hyperlipidemia is middle and old age hypertension patient's a common complication, and there have rising of report hypertension and T-CHOL and hdl level to reduce to be closely related, and metabolism disorder of blood lipid obviously increases cardiovascular diseases's danger and sickness rate.
The hyperpietic generally needs long-term prescription, in order to increase curative effect, reduces the untoward reaction that long-term prescription produces; Clinically drug combinations that adopt more; The scheme that drug combination adopts thiazide diuretic and beta-blocker to share as basic medicine and other depressor more, though these schemes have many advantages, life-time service still has many weak points; Can cause multiple dysbolismus like diuretic, like hypokalemia, hyperglycemia, hyperlipidemia etc.; Beta-blocker also has many untoward reaction, as cardiac muscle suppress, blood fat increases, drug withdrawal syndrome etc.
Taurine is the non-essential amino acid of body, and its toxicity is extremely low, take for a long time body influence little, but also the effect of nutritious body.Low dose of taurine is usually used in analgesic, calm, paroxysmal pain.Be used for the treatment of child and children's cold more.
Candesartan Cilexetil is the antihypertensive drugs of Japanese military field medicine Co., Ltd. research and development; Chemical name is (±)-1-[[(hexamethylene oxo) carbonyl] oxo] ethyl-2-ethyoxyl-1-[[2 '-(1H-tetrazole base-5)-[1,1 '-xenyl]-4-yl] methyl]-1H-benzimidazole-7-carboxylate.Candesartan Cilexetil is the precursor medicine of Candesartan, during gastrointestinal absorption, promptly rapidly, fully is being hydrolyzed to Candesartan, and hypotensive effect is obvious, and few side effects is a widely used clinically line antihypertensive drugs.
The inventor finds that unexpectedly the compatibility of candesartan Cilexetil and taurine can effectively reduce blood pressure, can reduce the generation of hypertension complication again, and unexpected synergism has taken place both compatibilities.
Goal of the invention: the purpose of this invention is to provide the hypertensive compound medicament composition of a kind of treatment, said composition can effectively reduce blood pressure, reduces the possibility that hypertension complication takes place.
Technical scheme of the present invention is: a kind of compound medicament composition of treating vascular hypertension is characterized in that containing candesartan Cilexetil and taurine.
Optimized technical scheme of the present invention is to contain candesartan Cilexetil 4-12mg in the compositions of UD, taurine 0.4 to 15 gram.
Optimized technical scheme of the present invention is to contain candesartan Cilexetil 6-8mg in the compositions of UD, taurine 1 to 10 gram.
Optimized technical scheme of the present invention is to contain candesartan Cilexetil 6-8mg in the compositions of UD, taurine 2.5 to 8 grams.
Optimized technical scheme of the present invention is to contain candesartan Cilexetil 6-8mg in the compositions of UD, taurine 3 to 6 grams.
The preferred technical scheme of the present invention is to contain candesartan Cilexetil 6mg-8mg in the compositions of UD, taurine 4 grams.
The preferred technical scheme of the present invention is to contain candesartan Cilexetil 6mg-8mg in the compositions of UD, taurine 6 grams.
The preferred technical scheme of the present invention is to contain candesartan Cilexetil 6mg-8mg in the compositions of UD, taurine 8 grams.
The present composition is pressed the employing pharmaceuticals industry adjuvant commonly used and the conventional method preparation of pharmaceutical industry.The mode of taking of the present composition is oral, is advisable with granule.
The invention has the beneficial effects as follows: through the reasonable compatibility of candesartan Cilexetil and taurine, produced beyond thought synergism, obtained a kind of compositions that can effectively bring high blood pressure down and can prevent the hypertension complication generation.
The instructions of taking that the present composition is suitable is oral, once-a-day, and one time one bag.
Embodiment 1, prescription:
Candesartan Cilexetil 4g, taurine 15000 grams, lactose 55 grams, differential silica gel 5 grams, mix homogeneously, 10% hydroxypropyl emthylcellulose, 80% ethanol liquid are as binding agent, and fluidized bed prilling is packed as 1000 bag granules.
Embodiment 2, prescription:
Candesartan Cilexetil 12g, taurine 400 grams, lactose 55 grams, differential silica gel 5 grams, mix homogeneously, 10% hydroxypropyl emthylcellulose, 80% ethanol liquid are as binding agent, and fluidized bed prilling is packed as 1000 bag granules.
Embodiment 3, prescription:
Candesartan Cilexetil 6g, taurine 10000 grams, lactose 55 grams, differential silica gel 5 grams, mix homogeneously, 10% hydroxypropyl emthylcellulose, 80% ethanol liquid are as binding agent, and fluidized bed prilling is packed as 1000 bag granules.
According to the amount of candesartan Cilexetil in the following table and taurine, press adjuvant amount and the method for preparing of embodiment 1 and accomplish embodiment 4～13.
| Embodiment | Candesartan Cilexetil, g | Taurine, g |
| 4 | 6 | 1500.0 |
| 5 | 8 | 2500.0 |
| 6 | 6 | 8000.0 |
| 7 | 6 | 6000.0 |
| 8 | 8 | 3000.0 |
| 9 | 6 | 3000.0 |
| 10 | 6 | 4000.0 |
| 11 | 8 | 5000.0 |
| 12 | 8 | 7000.0 |
| 13 | 8 | 8000.0 |
Test Example 1, case selection: outpatient service and the 25-60 that is in hospital the year middle and high degree hyperpietic totally 160 examples, male's 95 examples wherein, women's 65 examples, obey stable dose after SiDBP be 95-109mmHg (1mmHg=0.133kPa), seat systolic pressure 180mmHg.Exclusion standard: secondary hypertension, the cardiovascular and cerebrovascular disease history of attack is arranged, the arrhythmia that need heal with medicine, irritated to ingredient, drug dependence or alcoholic, gestation and age of sucking, severe hepatic, renal insufficiency.
Research method
To be selected in the patient and be divided into 8 groups at random, every group 20 people.All stop using 1 week of antihypertensive drugs before the test.1 group, take candesartan Cilexetil tablet (our company's product), the 8mg/ sheet, once-a-day; Take taurine (our company's product) for 2 groups, the 15g/ bag, once-a-day.3～7 groups of products of taking embodiment 1, embodiment 2, embodiment 4, embodiment 8, embodiment 9, embodiment 10 respectively, once-a-day, one time one bag.
Observation index:
Every at a distance from measuring patient seat right upper extremity blood pressure 1 time half an hour before Drug therapy begins after the drug withdrawal, continuous measurement 3 times is averaged as the basic blood pressure before the treatment; Measuring patient seat right upper extremity blood pressure 1 time weekly during the treatment was taken medicine for 8 weeks altogether, got its meansigma methods and was treatment back blood pressure.
Efficacy of antihypertensive treatment is judged: the hypertension efficacy assessment standard with reference to the unified regulation of Ministry of Public Health carries out efficacy evaluation.
Produce effects: diastolic pressure descends greater than 10mmHg, and reduces to normal; Or diastolic pressure descends greater than 20mmHg.
Effectively: diastolic pressure descends less than 10mmHg, but has reached normal; Or diastolic pressure decline 10-19mmHg; Or systolic pressure descends greater than 30mmHg.
Invalid: as not reach above-mentioned standard.
Total effective rate (%)=(produce effects example number+effective routine number)/total routine number * 100%
Table 1 treatment 8 all blood pressure
Table 2 is respectively organized patient's efficacy of antihypertensive treatment relatively
| Group | The example number | Produce effects | Effectively | Invalid | Total effective rate % |
| 1 | 20 | 8 | 9 | 3 | 85 |
| 2 | 20 | 5 | 9 | 6 | 70 |
| 3 | 20 | 8 | 11 | 1 | 95 |
| 4 | 20 | 10 | 10 | 0 | 100 |
| 5 | 20 | 10 | 10 | 0 | 100 |
| 6 | 20 | 10 | 10 | 0 | 100 |
| 7 | 20 | 8 | 12 | 0 | 100 |
| 8 | 20 | 12 | 8 | 0 | 100 |
Relatively can find through above test data,, improve the hypertensive effective percentage of treatment, produce beyond thought synergism through the drug combination of candesartan Cilexetil and taurine.
Test Example 2
Case selection: outpatient service and the 40-60 that is in hospital the year hypertension companion hyperlipemic patients totally 100 examples, male's 55 examples wherein, women's 45 examples.The disease of not having other cardiovascular and kidney aspect.
Research method
To be selected in the patient and be divided into 4 groups at random, every group 25 people.Take the candesartan Cilexetil medicine before participating in test, do not take other drug.Before test, before the beginning, get the morning of venous samples can before the meal, measure cholesterol and triglyceride, average as the basic numerical value before the treatment.1 group, take candesartan Cilexetil tablet (our company's product), the 8mg/ sheet, once-a-day; Take taurine (our company's product) for 2 groups, 15g/ day, once-a-day.3 groups of products of taking embodiment 2,4 groups of medicines of taking embodiment 10, light diet.After taking three months, part patient's ablation experiment group is got the morning of the venous samples can before the meal of still staying the test group patient, measures cholesterol and triglyceride, averages as the numerical value after the test.Data record is in table 3 before and after the test.
Blood fat is measured situation before and after table 3 test
Result of the test shows: the present composition has played the effect of beyond thought blood fat reducing.
Claims (8)
1. a compound medicament composition is characterized in that containing candesartan Cilexetil and taurine.
2. the said compositions of claim 1 is characterized in that containing candesartan Cilexetil 4-12mg, taurine 0.4 to 15 gram in the compositions of UD.
3. the said compositions of claim 1 is characterized in that containing candesartan Cilexetil 6-8mg, taurine 1 to 10 gram in the compositions of UD.
4. the said compositions of claim 1 is characterized in that containing candesartan Cilexetil 6-8mg, taurine 2.5 to 8 grams in the compositions of UD.
5. the said compositions of claim 1 is characterized in that containing candesartan Cilexetil 6-8mg, taurine 3 to 6 grams in the compositions of UD.
6. the said compositions of claim 1 is characterized in that containing candesartan Cilexetil 6mg-8mg, taurine 4 grams in the compositions of UD.
7. the said compositions of claim 1 is characterized in that containing candesartan Cilexetil 6mg-8mg, taurine 6 grams in the compositions of UD.
8. the said compositions of claim 1 is characterized in that containing candesartan Cilexetil 6mg-8mg, taurine 8 grams in the compositions of UD.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100670964A CN102600140A (en) | 2012-03-09 | 2012-03-09 | Composite for treating vascular hypertension |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012100670964A CN102600140A (en) | 2012-03-09 | 2012-03-09 | Composite for treating vascular hypertension |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102600140A true CN102600140A (en) | 2012-07-25 |
Family
ID=46518168
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012100670964A Pending CN102600140A (en) | 2012-03-09 | 2012-03-09 | Composite for treating vascular hypertension |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102600140A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140206674A1 (en) * | 2013-01-22 | 2014-07-24 | Boehringer Ingelheim International Gmbh | Combinations with 2-aminoethanesulfonic acid |
| CN111557933A (en) * | 2020-05-27 | 2020-08-21 | 北京康立生医药技术开发有限公司 | Composition for promoting absorption of taurine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008109170A1 (en) * | 2007-03-08 | 2008-09-12 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical composition comprising candesartan cilexetil |
| CN102309480A (en) * | 2011-09-26 | 2012-01-11 | 沈阳药科大学 | Compound antihypertensive pharmaceutical composition and preparation method thereof |
-
2012
- 2012-03-09 CN CN2012100670964A patent/CN102600140A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008109170A1 (en) * | 2007-03-08 | 2008-09-12 | Teva Pharmaceutical Industries Ltd. | Pharmaceutical composition comprising candesartan cilexetil |
| CN102309480A (en) * | 2011-09-26 | 2012-01-11 | 沈阳药科大学 | Compound antihypertensive pharmaceutical composition and preparation method thereof |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140206674A1 (en) * | 2013-01-22 | 2014-07-24 | Boehringer Ingelheim International Gmbh | Combinations with 2-aminoethanesulfonic acid |
| WO2014114627A1 (en) * | 2013-01-22 | 2014-07-31 | Boehringer Ingelheim International Gmbh | Combinations with 2-aminoethanesulfonic acid |
| JP2016505628A (en) * | 2013-01-22 | 2016-02-25 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Combination with 2-aminoethanesulfonic acid |
| US10918612B2 (en) * | 2013-01-22 | 2021-02-16 | Markus Zwickl | Combinations with 2-aminoethanesulfonic acid |
| CN111557933A (en) * | 2020-05-27 | 2020-08-21 | 北京康立生医药技术开发有限公司 | Composition for promoting absorption of taurine |
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Application publication date: 20120725 |